Agnieszka Madej-Pilarczyk

Second University of Naples, Caserta, Campania, Italy

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Publications (16)23.81 Total impact

  • International journal of cardiology 03/2014; · 7.08 Impact Factor
  • Anna Fidzianska, Agnieszka Madej-Pilarczyk, Irena Hausmanowa-Petrusewicz
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    ABSTRACT: Congenital fiber type disproportion with delayed fiber type maturation and the appearance of cap structures were analyzed in a child with p.Arg168Gly mutation in TPM3 gene. Very narrow myotube-like Type 1 fibers with single nuclei decorated by cap structures seem to be a result of a failure in fusion process and mature fiber formation. Repeated mutations in exon 5 of TPM3 gene giving cap structures may be a different consequence of the loss of specific isoform normally operating in the fusion process and sarcomer formation.
    Clinical neuropathology 08/2013; · 1.34 Impact Factor
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    ABSTRACT: Lamins (LMNA) are the main proteins of the nuclear lamina considered to be the ancestors of all intermediate filament proteins. They form complex protein assemblies with integral proteins of the inner nuclear membrane, transcriptional regulators, histones and chromatin modifiers. During recent years, interest in lamins has greatly increased due to the identification of many distinct heritable human disorders associated with lamin mutations. These disorders, collectively termed laminopathies, range from muscular dystrophies to premature aging. They may affect muscle, fat, bone, nerve and skin tissues. The workshop was addressed to understand lamin organization and its roles in nuclear processes, mutations in lamins affecting cell and tissues functions, the biology of the nucleus and laminopathic disease mechanisms, all aspects important for designing future therapies.
    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 05/2013; 32(1):18-22.
  • Anna Fidzianska, Agnieszka Madej-Pilarczyk, Ewa Walczak, Marek Kuch
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    ABSTRACT: Background Danon disease is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2).Materials and Methods Our study describes a 19-year-old man with isolated hypertrophic cardiomyopathy, in whom we performed DNA analysis and compared results of microscopic analysis of skeletal and cardiac muscles.Results Sequencing of the LAMP-2 gene revealed a novel point mutation c.137G > A in exon 2, leading to premature stop codon. Ultrastructural analysis of cardiac and skeletal muscles revealed the presence of unusual autophagic vacuoles in both. Although some vacuoles in skeletal muscle reacted strongly with dystrophin, β-sarcoglycan, and laminin, those in cardiomyocytes showed no immunoreactivity.Conclusion Our immunohistochemical and ultrastructural findings reinforce the claim that in Danon disease the pathomechanism of chaperone-mediated autophagy in cardiomyocytes differs from that in skeletal muscle.
    Neuropediatrics 03/2013; · 1.19 Impact Factor
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    ABSTRACT: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615_1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 01/2013; · 2.01 Impact Factor
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    ABSTRACT: Introduction: During human myogenesis and synaptogenesis, the first contact between multiaxonal nerve terminals and the primary myotube occurs at an early stage of gestation, then monoaxonal nerve terminals form and postsynaptic clusters of acetylcholine-receptor are modified and redistributed to the site of muscle-nerve contact. The aim of this study is to present the ultrastructural features of muscle and motor-junction immaturity severe enough to lead to death in the first months of life. Material and methods: Ultrastructural-level analysis was carried out on the quadriceps femoris muscle of an infant born at full term with severe respiratory distress but with normal SMN1 and IGHMBP2 genes. Results: Arrested muscle maturation was manifested in the presence of primary and mature myotubes, prepatterned acetylcholine-receptor clusters devoid of terminal axons, lack of synapses and multiaxonal unmyelinated intramuscular nerves. Conclusion: The "naked" prepatterned clusters observed on the surface of myotubes normally never observed in neonates might be a sign of a new genetic defect in innervation.
    Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. 01/2013; 51(4):319-23.
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    ABSTRACT: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies--X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.
    Scandinavian journal of clinical and laboratory investigation 12/2011; 71(8):658-62. · 1.38 Impact Factor
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    ABSTRACT: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is of diagnostic and prognostic value in different heart diseases. One such dilated cardiomyopathy (DCM) with conduction disturbances is one of the most serious manifestations in Emery-Dreifuss muscular dystrophy (EDMD). Herein we therefore detail work to evaluate the potential significance of circulating TN-C in patients with EDMD, speculating that it may define the cardiac dysfunction, especially in patients who may be cardiac asymptomatic, but still be at risk of sudden death. Serum levels of TN-C were quantified by sandwich immunoassay ELISA in 25 EDMD patients (10 with laminopathy-AD-EDMD and 15 with emerinopathy-X-EDMD), 8 X-EDMD carriers, 9 disease controls (patients with dystrophinopathy), and 15 age-matched healthy controls. Fourteen of the EDMD patients had repeated TN-C examinations after 3 to 7 years. The levels of circulating TN-C were elevated in AD-EDMD and X-EDMD patients, as well as in some X-EDMD carriers, and patients with dystrophinopathy. The correlation between the TN-C level and left end-systolic ventricle diameter (LVDD) was significant in X-EDMD, while those with left atrium diameter (LAD) and the ejection fraction (EF) were not. In "follow-up" studies TN-C levels were not found to change over time in AD-EDMD, while rising in X-EDMD. The presented results indicate that assessments of circulating TN-C levels may help to identify EDMD patients at risk of dilated cardiomyopathy. TN-C might therefore be considered a candidate for a new biomarker, useful in detecting of cardiomyopathy and in further monitoring of the DCM therapy in patients with EDMD.
    Clinica chimica acta; international journal of clinical chemistry 08/2011; 412(17-18):1533-8. · 2.54 Impact Factor
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    ABSTRACT: Familial partial lipodystrophy (FPLD) belongs to the family of laminopathies - disorders associated with mutation in the lamin A/C gene (LMNA). FPLD is characterized by loss of subcutaneous adipose tissue from the limbs, trunk and buttocks, with its concomitant accumulation on the face, neck and intra-abdominal region, and by metabolic disorders. We present the first Polish family with FPLD confirmed genetically. A 34-year-old woman admitted with myalgia and cushingoid appearance was found to have a round face with double chin, neck bump, and loss of fat on extremities. Diagnostic tests revealed impaired glucose tolerance and increased levels of liver enzymes, and ultrasonography revealed hepatic steatosis. Her 9-year-old daughter presented a similar phenotype, but no fat loss. A genetic test revealed the presence of a heterozygous LMNA gene mutation: c.1445G>A, consistent with the "hot spot" for FPLD. Treatment with metformin to improve insulin resistance and address the diabetes proved successful.
    Neurologia i neurochirurgia polska 01/2010; 44(3):291-6. · 0.49 Impact Factor
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    ABSTRACT: The study demonstrates a 12-year-old patient with progressive proximal muscle weakness, joint contractures, rigidity of the neck, and absence of emerin and lamin A in the muscle nuclei, which is caused by intronic mutation IVS3-27del18 (c.266-27del18) in the emerin gene. The most surprising finding was the appearance of IBM-like inclusions in euchromatin, as well as aberrant nuclei. It may be speculated that altered expression of the emerin-lamin complex and modification of the nuclear matrix leads to formation of tubulofilamentous structures in the presented case.
    Clinical neuropathology 01/2010; 29(2):78-83. · 1.34 Impact Factor
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    ABSTRACT: In the pathogenesis of dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD) matrix metalloproteinases (MMPs) are supposed to be involved and may have diagnostic/prognostic value. Serum levels of MT1-MMP, MMP-2 and MMP-9 were quantified by ELISA and zymography in 22 EDMD patients and 15 age-matched controls. In the autosomal-dominant EDMD MMP-2 and MT1-MMP were increased in all cases, and MMP-9 was increased in two of the eight examined patients. In the X-linked EDMD MMP-2 expression was increased in all the cases, MMP-9 level was elevated in 3 of the 14 cases, and MT1-MMP was decreased in eight of these patients. There was no evident correlation between the MMPs level and the different cardiac parameters including left-ventricular end-diastolic diameter, left atrial diameter and left ventricular ejection fraction in either form of EDMD. The presented results indicate that a changed level of matrix metalloproteinases, especially that of MMP-2 in serum, may be of value for detection of cardiac involvement in EDMD patients, especially in those patients with no evident subjective cardiac symptoms. Further follow-up studies of MMPs are needed to check if their determination is of value for monitoring of the progression of atrial/ventricular dilatation. MMPs determinations may also be useful for monitoring DCM treatment by synthetic MMPs inhibitors.
    Acta biochimica Polonica 12/2009; 56(4):717-22. · 1.19 Impact Factor
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    ABSTRACT: Hutchinson-Gilford progeria is a rare genetic disorder resulting from mutations in the LMNA gene encoding lamin A/C. In addition to the classical phenotype usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid syndromes have been described. They have some distinct features, such as skeletal deformities or scleroderma-like skin changes. The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE-24. We present a 2-year-old girl born to consanguineous parents affected by progeroid syndrome with scleroderma-like skin changes. Genetic analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same heterozygous mutation was found in the patient's parents and 11 other family members. The progeroid syndrome in our patient shares the signs of two laminopathies: progeria and restrictive dermatopathy. Two other children in the family died at the age of 2 due to a disease similar to that in the proposita. On the basis of the family pedigree we presume that these children probably had the same homozygous LMNA mutation. Scleroderma-like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations.
    American Journal of Medical Genetics Part A 11/2009; 149A(11):2387-92. · 2.30 Impact Factor
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    ABSTRACT: We present a 6-year-old girl with premature aging associated with mild myopathy, displaying muscle weakness, joint contractures and hyporeflexia. Genetic analysis revealed rare heterozygous point mutation in lamin A/C gene, g.428C>T. Cardiological evaluation showed atrial fibrillation, but we did not find signs of coronary heart disease, which is life-threatening cardiovascular complication in progeria. Electron microscopy of the muscle revealed abnormalities in nuclear architecture, i.e. blebbing, thick lamina and peripheral distribution of heterochromatin. As some diagnostic criteria characteristic for classic progeria are not fulfilled, this case could be regarded as atypical progeria associated with myopathy and atrial fibrillation. To our knowledge, this is the second case of such association described in the literature.
    European Journal of Paediatric Neurology 03/2008; 12(5):427-30. · 1.98 Impact Factor
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    I Hausmanowa-Petrusewicz, A Madej-Pilarczyk
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    ABSTRACT: This paper is a part of an introduction to authors' study on systemic laminopathies and their role in human aging. Of special interest is progeria--a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging--Werner's syndrome.
    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 10/2007; 26(2):101-4.
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    ABSTRACT: Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disorder caused by mutations of the SMN1 gene. Because of the autosomal recessive type of transmission, the genetic risk of the disease in the following generations is small and is estimated to be about 1%. Here we present a case report of a father and son suffering from SMA. The father is affected with a mild form of SMA, with onset at about 13 years of age. The son suffers from SMA type 2, with onset at about 13 months of age. In both father and son, genetic analysis showed biallelic deletion of exons 7 and 8 in the SMN1 gene. The boy's mother is a carrier of the deletion at the SMA locus. Quantitative analysis revealed one copy of the SMN1 gene.
    Neurologia i neurochirurgia polska 40(5):446-9. · 0.49 Impact Factor
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    ABSTRACT: The authors present the results of a 4-year follow-up of patients with Emery-Dreifuss dystrophy (EDMD) included in a project on laminopathies. The focus of the discussion is on the clinical and genetic characteristics, and the classification of the two forms of Emery-Dreifuss dystrophy [i.e. associated with either emerinopathy (EDMD1) or laminopathy (EDMD2)]. The study includes 37 patients from 12 families with EDMD, 28 having emerinopathy and 9 with laminopathy. On the basis of findings from clinical examination and laboratory tests (24-hour ECG monitoring, echocardiography, histological and immunohistochemical studies of muscle), the authors describe phenotypes of the two forms of Emery-Dreifuss dystrophy, the natural course of the disease, and a possible severe cardiovascular involvement which may lead to severe cardiac complications and sudden death. The patients with EDMD were treated mainly by cardiologists. Besides symptomatic management, implantation of a cardiac pacemaker or cardioverter-defibrillator is often required. The intrafamilial and interfamilial variability of laminopathies is discussed in relation to interactions between nuclear proteins. Since the EDMD carrier state in females is associated with cardiac symptoms (without skeletal muscle involvement), systematic cardiological supervision is indicated. Likewise, there are certain patients presenting a typical EDMD phenotype in which no mutations in the EMD or LMNA genes can be confirmed. This may indicate that an Emery-Dreifuss-like dystrophy could also be associated with mutations in other genes.
    Neurologia i neurochirurgia polska 43(5):415-20. · 0.49 Impact Factor

Publication Stats

20 Citations
1 Download
23.81 Total Impact Points


  • 2013
    • Second University of Naples
      Caserta, Campania, Italy
  • 2011
    • Mossakowski Medical Research Centre Polish Academy of Sciences
      Ochotnica, Lesser Poland Voivodeship, Poland
  • 2007–2011
    • Polish Academy of Sciences
      • Neuromuscular Unit
      Warsaw, Masovian Voivodeship, Poland
  • 2010
    • Medical University of Warsaw
      • Katedra i Klinika Neurologii
      Warsaw, Masovian Voivodeship, Poland